Document Type : Review Article
Authors
1 Msc molecular Genetics, Islamic Azad university Central Tehran Branch, Tehran, Iran
2 School of Paramedical Sciences, Iran University of Medical Sciences, Tehran, Iran
Abstract
Humans are continuously exposed to a wide of carcinogenic and mutagenic stimuli, including environmental toxins, radiation and viruses as well as other infections. Tumor metastasis is responsible for approximately 9% of all cancer related deaths. The tumor microenvironment (TME) contains many distinct cell types, including endothelial cells and their precursors, pericytes, smooth muscle cells, fibroblasts, carcinoma-associated fibroblasts, myofibroblasts, neutrophils, eosinophils, basophils, mast cells, T and B lymphocytes, natural killer cells and antigen presenting cells (APC) such as macrophages and dendritic cells. Recent evidence has shown that stromal tissue is much more than a passive bystander in the development and progression of cancers. None the lese,the clinical therapy for many types of human cancers has mainly focused on the malignant cancer cell itself, and have made great achievements, yet cancer therapy still remains a great challenge. This review highlights the evidence for the crucial role of the tumor microenvironment in tumor progression and metastasis.
Keywords
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metastasis. Nature Reviews Immunology. 2015 Feb;15(2):73-
86.
3.McAllister SS, Weinberg RA. The tumour-induced systemic
environment as a critical regulator of cancer progression and
metastasis. Nature cell biology. 2014 Aug;16(8):717-27.
4.Neophytou CM, Pierides C, Christodoulou MI, Costeas P, Kyriakou
TC, Papageorgis P. The role of tumor-associated myeloid cells
in modulating cancer therapy. Frontiers in Oncology. 2020 Jun
9;10:899.
5.Kockx MM, McCleland M, Koeppen H. Microenvironmental
regulation of tumour immunity and response to immunotherapy.
The Journal of Pathology. 2021 Jul 1 6.Joyce JA, Pollard JW.
Microenvironmental regulation of metastasis. Nature reviews
cancer. 2009 Apr;9(4):239-52.
7.Quail DF, Joyce JA. Microenvironmental regulation of
tumor progression and metastasis. Nature medicine. 2013
Nov;19(11):1423-37.
8.Stoll EA, Horner PJ, Rostomily RC. The impact of age on oncogenic
potential: tumor‐initiating cells and the brain microenvironment.
Aging Cell. 2013 Oct;12(5):733-41.
9.Fülöp T, Larbi A, Kotb R, Pawelec G. Immunology of Aging and
Cancer Development. Manag. Aging. 2013;38:38-48.
10.Hofseth LJ, Wargovich MJ. Inflammation, cancer, and targets of
ginseng. The Journal of nutrition. 2007 Jan 1;137(1):183S-5S.
11.Allavena P, Sica A, Solinas G, Porta C, Mantovani A. The
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of tumor-associated macrophages. Critical reviews in oncology/
hematology. 2008 Apr 1;66(1):1-9.
12.Barcellos-Hoff MH, Park C, Wright EG. Radiation and the
microenvironment–tumorigenesis and therapy. Nature Reviews
Cancer. 2005 Nov;5(11):867-75.
13.Benelli R, Lorusso G, Albini A, Noonan DM. Cytokines and
chemokines as regulators of angiogenesis in health and disease.
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cancer. Nature Reviews Cancer. 2006 Jul;6(7):506-20.
15.Onal S, Turker-Burhan M, Bati-Ayaz G, Yanik H, Pesen-Okvur
D. Breast cancer cells and macrophages in a paracrine-juxtacrine
loop. Biomaterials. 2021 Jan 1;267:120412
16.Osmanian C, Jacks T. Hypoxia-mediated selection of cells
with diminished apoptotic potential in solid tumors. Nature.
1996;379(6560):88-91.
17.Goswami S, Sahai E, Wyckoff JB, Cammer M, Cox D, Pixley
FJ, Stanley ER, Segall JE, Condeelis JS. Macrophages promote
the invasion of breast carcinoma cells via a colony-stimulating
factor-1/epidermal growth factor paracrine loop. Cancer
research. 2005 Jun 15;65(12):5278-83.
18.Joyce JA, Baruch A, Chehade K, Meyer-Morse N, Giraudo E,
Tsai FY, Greenbaum DC, Hager JH, Bogyo M, Hanahan D.
Cathepsin cysteine proteases are effectors of invasive growth
and angiogenesis during multistage tumorigenesis. Cancer cell.
2004 May 1;5(5):443-53.
19.Lewis C, Murdoch C. Macrophage responses to hypoxia:
implications for tumor progression and anti-cancer therapies.
The American journal of pathology. 2005 Sep 1;167(3):627-35.
20.Cai X, Yin Y, Li N, Zhu D, Zhang J, Zhang CY, Zen K.
Re-polarization of tumor-associated macrophages to pro-
inflammatory M1 macrophages by microRNA-155. Journal of
molecular cell biology. 2012 Oct 1;4(5):341-3.
21.Almand B, Clark JI, Nikitina E, van Beynen J, English NR,
Knight SC, Carbone DP, Gabrilovich DI. Increased production
of immature myeloid cells in cancer patients: a mechanism of
immunosuppression in cancer. The Journal of Immunology.
2001 Jan 1;166(1):678-89.
22.Orimo A, Weinberg RA. Stromal fibroblasts in cancer: a novel
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601.
23.Hanahan D, Coussens LM. Accessories to the crime: functions
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24.Cornil I, Theodorescu D, Man S, Herlyn M, Jambrosic J, Kerbel
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S, Spandidos DA, Libra M. The tumor microenvironment in
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2012 Jun 1;40(6):1733-47.
26.Rattigan Y, Hsu JM, Mishra PJ, Glod J, Banerjee D. Interleukin
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hypoxic tumor milieu. Experimental cell research. 2010 Dec
10;316(20):3417-24.
27.Grum-Schwensen B, Klingelhöfer J, Grigorian M, Almholt K,
Nielsen BS, Lukanidin E, Ambartsumian N. Lung metastasis
fails in MMTV-PyMT oncomice lacking S100A4 due to a
T-cell deficiency in primary tumors. Cancer research. 2010 Feb
1;70(3):936-47.
28.Pollard JW. Macrophages define the invasive microenvironment
in breast cancer. Journal of leukocyte biology. 2008
Sep;84(3):623-30.
29.Allavena P, Sica A, Garlanda C, Mantovani A. The Yin‐Yang
of tumor‐associated macrophages in neoplastic progression
and immune surveillance. Immunological reviews. 2008
Apr;222(1):155-61.
30.Bingle L, Lewis CE, Corke KP, Reed MW, Brown NJ.
Macrophages promote angiogenesis in human breast tumour
spheroids in vivo. British journal of cancer. 2006 Jan;94(1):101-
7.
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Molecular Sciences. 2021 Jan;22(18):9926.
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39.Romagnani P, Lasagni L, Annunziato F, Serio M, Romagnani S.
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promoted by chronic inflammation is B lymphocyte dependent.
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27.Grum-Schwensen B, Klingelhöfer J, Grigorian M, Almholt K,
Nielsen BS, Lukanidin E, Ambartsumian N. Lung metastasis
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T-cell deficiency in primary tumors. Cancer research. 2010 Feb
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28.Pollard JW. Macrophages define the invasive microenvironment
in breast cancer. Journal of leukocyte biology. 2008
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of tumor‐associated macrophages in neoplastic progression
and immune surveillance. Immunological reviews. 2008
Apr;222(1):155-61.
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Macrophages promote angiogenesis in human breast tumour
spheroids in vivo. British journal of cancer. 2006 Jan;94(1):101-
7.
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and soil’hypothesis revisited. Nature reviews cancer. 2003
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32.Ioannidou E, Moschetta M, Shah S, Parker JS, Ozturk MA,
Pappas-Gogos G, Sheriff M, Rassy E, Boussios S. Angiogenesis
and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms
of Action and Molecular Targets. International Journal of
Molecular Sciences. 2021 Jan;22(18):9926.
33.Joseph IB, Isaacs JT. Macrophage role in the anti-prostate cancer
response to one class of antiangiogenic agents. Journal of the
National Cancer Institute. 1998 Nov 4;90(21):1648-53.
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by heregulin β1 and CXCL12. Cancer research. 2009 Apr
1;69(7):3221-7.
35.Wai PY, Kuo PC. Osteopontin: regulation in tumor metastasis.
Cancer and Metastasis Reviews. 2008 Mar;27(1):103-18.
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attenuates tumor growth and metastasis. Proceedings of the
National Academy of Sciences. 1998 Aug 4;95(16):9325-30.
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J, Serre CM, Grès S, Bendriss-Vermare N, Bollen M, Saez S.
Cancer cell expression of autotaxin controls bone metastasis
formation in mouse through lysophosphatidic acid-dependent
activation of osteoclasts. PloS one. 2010 Mar 17;5(3):e9741.
38.Tuxhorn JA, McAlhany SJ, Yang F, Dang TD, Rowley DR.
Inhibition of transforming growth factor-β activity decreases
angiogenesis in a human prostate cancer-reactive stroma
xenograft model. Cancer research. 2002 Nov 1;62(21):6021-5.
39.Romagnani P, Lasagni L, Annunziato F, Serio M, Romagnani S.
CXC chemokines: the regulatory link between inflammation and
angiogenesis. Trends in immunology. 2004 Apr 1;25(4):201-9.
40.Amirkhosravi A, Meyer T, Chang JY, Amaya M, Siddiqui F,
Desai H, Francis JL. Tissue factor pathway inhibitor reduces
experimental lung metastasis of B16 melanoma. Thrombosis
and haemostasis. 2002;87(06):930-6.
41.Landsberg J, Kohlmeyer J, Renn M, Bald T, Rogava M, Cron M,
Fatho M, Lennerz V, Wölfel T, Hölzel M, Tüting T. Melanomas
resist T-cell therapy through inflammation-induced reversible
dedifferentiation. Nature. 2012 Oct;490(7420):412-6.
42.Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod
R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil
GS, Yamada SD. Adipocytes promote ovarian cancer metastasis
and provide energy for rapid tumor growth. Nature medicine.
2011 Nov;17(11):1498-503.
43.Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of
myeloid cells in the promotion of tumour angiogenesis. Nature
reviews cancer. 2008 Aug;8(8):618-31.
44.de Caestecker MP, Piek E, Roberts AB. Role of transforming
growth factor-β signaling in cancer. Journal of the National
Cancer Institute. 2000 Sep 6;92(17):1388-402.
45.Nakai Y, Isayama H, Ijichi H, Sasaki T, Takahara N, Ito Y,
Matsubara S, Uchino R, Yagioka H, Arizumi T, Hamada T.
A multicenter phase II trial of gemcitabine and candesartan
combination therapy in patients with advanced pancreatic cancer:
GECA2. Investigational new drugs. 2013 Oct;31(5):1294-9.
46.Feng S, Agoulnik IU, Bogatcheva NV, Kamat AA, Kwabi-Addo
B, Li R, Ayala G, Ittmann MM, Agoulnik AI. Relaxin promotes
prostate cancer progression. Clinical Cancer Research. 2007
Mar 15;13(6):1695-702.
47.Duda DG, Duyverman AM, Kohno M, Snuderl M, Steller EJ,
Fukumura D, Jain RK. Malignant cells facilitate lung metastasis
by bringing their own soil. Proceedings of the National Academy
of Sciences. 2010 Dec 14;107(50):21677-82.
48.Moriggi G, Falzacappa CV, Mangialardo C, Michienzi S,
Stigliano A, Brunetti E, Toscano V, Misiti S. Thyroid hormones
(T3 and T4): dual effect on human cancer cell proliferation.
Anticancer research. 2011 Jan 1;31(1):89-96.
49.Di Stefano JF, Kirchner M, Dagenhardt K, Hagag N. Activation
of cancer cell proteases and cytotoxicity by EGF and PDGF
growth factors. The American journal of the medical sciences.
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50.Peterson JE, Zurakowski D, Italiano Jr JE, Michel LV, Fox L,
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regulatory proteins in human platelets. American journal of
hematology. 2010 Jul;85(7):487-93.
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myeloid cells in the promotion of tumour angiogenesis. Nature
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